This is the first study that demonstrated MSANTD3 was valuable for HNSCC diagnosis and prognosis. On one hand, our analysis indicated that MSANTD3 was overexpressed in HNSCC compared with the normal head and neck tissues. This revealed the potential for using MSANTD3 for HNSCC diagnosis. We also found evidence from open data sets suggesting that the copy number of MSANTD3 in HNSCC was higher than that in normal tissues. We suggested that the higher copy number might account for the higher expression level of MSANTD3 mRNA, yet there might be other factors that can also contribute to the higher expression, such as transcriptional factor and methylations, which required further exploration. On the other hand, as shown in Fig. 2B, the overall survival rate of HNSCC patients was significantly different between MSANTD3 high and MSANTD3 low samples, indicating the association of overall survival and the expression of MSANTD3 in HNSCC tissues. The diagnostic and prognostic potential of MSANTD3 has been reported in other types of cancers. For example, in breast cancer, MSANTD3 was found overexpressed in cancer tissue than adjacent normal breast tissues . In non-small cell lung cancer, MSANTD3 was also identified as a biomarker that potentially affects therapeutic response in patients . In Fig. 3, high expression of MSANTD3 was associated with a worse prognosis and the prognosis of MSANTD3 was independent of age and pN stage. All these bioinformatic studies demonstrated the potential clinical value of MSANTD3 as a prognosis biomarker.
One of the most significant findings of this study was that we are the first study to report that MSANTD3 might increase HNSCC cell migration. The previous studies only reported the functional roles of MSANTD3 inside cells[5, 9], but little is known about its role in cell-cell interactions. Our DEGs enrichment study inferred a potential association of MSANTD3 and the regulation of the extracellular matrix, which is critical in cell migration and cancer metastasis. It has been reported that once HNSCC patients present with recurrence and/or metastasis, the median overall survival (OS) hardly exceeds 12 months , thus the migration of HNSCC cells has been one of the most concerns for HNSCC study. In this study, we collected clinical samples of metastasis HNSCC and primary HNSCC and compared the expression of MSANTD3. A commonly used QPCR and western blotting assay were conducted [18, 19], which suggested that MSANTD3 was overexpressed in the metastasis samples compared to primary samples.
One of the special of our study was we determined multiple cell lines. The correlation of HSCN1 expression and velocity of migration of the eight HNSCC cell lines we tested strongly suggested that MSANTD3 was a regulatory molecule for HNSCC cell migration. We validated the promoting effect of MSANTD3 on HNSCC cell migration by overexpressing MSANTD3 in YD-15 cells. These results were consistent with our hypothesis that MSANTD3 regulated cancer cell migration and metastasis. Furthermore, most of the previous studies investigated cancer cell migration using the wound-healing or the transwell assay , which determined the migration of a group of cancer cells as a whole. Our study was the first to investigate the role of MSANTD3 by tracking individual cell migration. Nevertheless, although we obtain the velocity of individual cell migration, we were not able to determine the expression of MSANTD3 in the cell we recorded. In addition, cancer cells might have different manners under in vivo or in-vitro conditions. Animal models have been widely used in research [21–23]. Further study should apply the in vivo orthotopic xenografts mice model to verify the role of MSANTD3 in HNSCC cell invasion and metastasis.
The potential regulation of MSANTD3 on cancer migration might contribute to the effects of these factors on cancers. Yet, further studies are required to identify the direct impact of MSANTD3 on cancer cell migration. This study aimed to validate the role of MSANTD3 in HNSCC cell migration, but the limitation of the study is that we only provided evidence supporting the functional effect of MSANTD3 on cancer cell migration, yet, the mechanisms underlying these effects were not clear. The enrichment analysis revealed several potential mechanisms, such as the PI3K − Akt signaling pathway, IL − 17 signaling pathway, and Estrogen signaling pathway, that required further validation with experimental evidence. In addition, as the enrichment data revealed that MSANTD3 might associate with the PI3K − Akt signaling pathway, which is the ion-homeostasis associated pathway[24, 25], many cancer-related ion channels, such as VGSC[26–28], TRP[29, 30], and TPCs[31, 32] might be involved. The role of most of these ion channels remains unclear and whether they contribute to the effects of MSANTD3 on cancer cells needs further investigation. In the clinical treatment of human disease, many different therapies might be applied. In cancer treatment, many drugs might directly or indirectly affect cancer metastasis by either regulated cancer cells or the immune system such as the use of anesthetics or traditional medicines [20, 34–40]. We think MSANTD3 can be a drug target candidate for general cancer but not only HNSCC.
In conclusion, this is the first study with HNSCC and MSANTD3. We demonstrated that 1) MSANTD3 is higher expressed in HNSCC than normal tissue and in metastatic than primary tumor; 2) cells with high MSANTD3 presented higher migration velocity; 3) the overexpression and knockdown of MSANTD3 interfered on cell migration; 4) further study should apply the in vivo orthotopic xenografts mice model to verify the role of MSANTD3 in HNSCC cell invasion and metastasis.